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11.
Tokuyuki Yoshida Kunihiko Morihiro Yuki Naito Atsushi Mikami Yuuya Kasahara Takao Inoue Satoshi Obika 《Nucleic acids research》2022,50(13):7224
Currently, gapmer antisense oligonucleotide (ASO) therapeutics are under clinical development for the treatment of various diseases, including previously intractable human disorders; however, they have the potential to induce hepatotoxicity. Although several groups have reported the reduced hepatotoxicity of gapmer ASOs following chemical modifications of sugar residues or internucleotide linkages, only few studies have described nucleobase modifications to reduce hepatotoxicity. In this study, we introduced single or multiple combinations of 17 nucleobase derivatives, including four novel derivatives, into hepatotoxic locked nucleic acid gapmer ASOs and examined their effects on hepatotoxicity. The results demonstrated successful identification of chemical modifications that strongly reduced the hepatotoxicity of gapmer ASOs. This approach expands the ability to design gapmer ASOs with optimal therapeutic profiles. 相似文献
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The ultrastructure of the purified and lyophilized endotoxin from Escherichia coli O111 was observed by ultrathin sectioning. Onion-like globular membrane structures were observed in addition to rod-like and ribbon-like structures, indicating the existence of a globular membrane structure even in the dried state. 相似文献
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Kazuo Imai Norihito Tarumoto Kiyoko Amo Makoto Takahashi Naoya Sakamoto Atsushi Kosaka Yasuyuki Kato Kei Mikita Jun Sakai Takashi Murakami Yutaka Suzuki Shigefumi Maesaki Takuya Maeda 《Parasitology international》2018,67(1):34-37
Cutaneous leishmaniasis (CL) is gaining attention as a public health problem. We present two cases of CL imported from Syria and Venezuela in Japan. We diagnosed them as CL non-invasively by the direct boil loop-mediated isothermal amplification method and an innovative sequencing method using the MinION? sequencer. This report demonstrates that our procedure could be useful for the diagnosis of CL in both clinical and epidemiological settings. 相似文献
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Masashi Yamada Hiroshi Ohnishi Shin-ichiro Sano Toshiyuki Araki Atsushi Nakatani Toshihiko Ikeuchi & Hiroshi Hatanaka 《Journal of neurochemistry》1999,73(1):41-49
Shp2, a protein tyrosine phosphatase possessing SH2 domains, is utilized in the intracellular signaling of various growth factors. Shp2 is highly expressed in the CNS. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, which also shows high levels of expression in the CNS, exerts neurotrophic and neuromodulatory effects in CNS neurons. We examined how BDNF utilizes Shp2 in its signaling pathway in cultured cerebral cortical neurons. We found that BDNF stimulated coprecipitation of several tyrosine-phosphorylated proteins with anti-Shp2 antibody and that Grb2 and phosphatidylinositol 3-kinase (PI3-K) were coprecipitated with anti-Shp2 antibody in response to BDNF. In addition, both anti-Grb2 and anti-PI3-K antibodies coprecipitated Shp2 in response to BDNF. The BDNF-stimulated coprecipitation of the tyrosine-phosphorylated proteins, Grb2, and PI3-K with anti-Shp2 antibody was completely inhibited by K252a, an inhibitor of TrkB receptor tyrosine kinase. This BDNF-stimulated Shp2 signaling was markedly sustained as well as BDNF-induced phosphorylation of TrkB and mitogen-activated protein kinases. In PC12 cells stably expressing TrkB, both BDNF and nerve growth factor stimulated Shp2 signaling similarly to that by BDNF in cultured cortical neurons. These results indicated that Shp2 shows cross-talk with various signaling molecules including Grb2 and PI3-K in BDNF-induced signaling and that Shp2 may be involved in the regulation of various actions of BDNF in CNS neurons. 相似文献
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Diurnal changes in needle gas exchange in alpine Pinus pumila during snow-melting and summer seasons
Atsushi Ishida Takashi Nakano Seikoh Sekikawa Emiko Maruta Takehiro Masuzawa 《Ecological Research》2001,16(1):107-116
Pinus pumila (Pallas) Regel. is a dominant dwarf tree in alpine regions of Japan. The possible factors limiting the net photosynthetic rate (Pn) of the needles of P. pumila were examined in the snow-melting (May) and the summer (August) seasons. In August, in situ maximum Pn was 20 mol kg–1 needle s–1 in the current-year needles and 25 mol kg–1 needle s–1 in the 1-year-old needles. Diurnal trends of Pn in August were positively related to fluctuations in photosynthetic photon flux density (PPFD) and no midday depression of Pn was found, indicating that a decrease in PPFD rather than an increase in needle-to-air vapor pressure deficit (W) might cause the reduction of Pn. Both stomatal conductance (gs) and Pn were lower in May than in August. In May, Pn and gs were almost zero in the morning, but gradually increased with decreasing W, reaching maximum Pn values (4 mol kg–1 needle s–1) and gs (60 mmol kg–1 needle s–1) at 16.00 hours. The daytime Pn in May was positively related to gs. Relative water content in the exposed needles above the snow in May was 83%, which was far above the lethal level. This indicates that the water flow from stems or soils to needles was enough to compensate for a small amount of water loss due to the low gs in May, although the water supplied to needles would be impeded by the low temperatures. Thus, the reduced gs in May would be important for avoiding needle desiccation, and would result in a reduced Pn. 相似文献
18.
Jae-Seong Lee Ryeo-Ok Kim Jae-Sung Rhee Jeonghoon Han Dae-Sik Hwang Beom-Soon Choi Chang Joo Lee Yong-Dal Yoon Jong-Sung Lim Young-Mi Lee Gyung Soo Park Atsushi Hagiwara Ik-Young Choi 《Hydrobiologia》2011,662(1):65-75
The monogonont rotifer, Brachionus ibericus (S type), is considered to be a promising model species for developmental biology, evolution, and environmental genomics. In an attempt to accelerate the molecular understanding of B. ibericus, we sequenced 680.5 Mb of genomic DNA using the genome sequencer GS-FLX-Titanium. We obtained 2,062,621 reads (average read length 329.9 bp) and 145,418 contigs (total contigs length 125.7 Mb) after excluding small reads (less than 200 bp) from the assembly, and finally obtained 10,133 unigenes (E value ?? 9.00E?04) after non-redundant (NR) BLAST search. In this article, we summarize the genomic DNA sequences of B. ibericus and discuss their potential use in the study of reproductive biology, endocrinology, environmental genomics, and ecotoxicological studies, and for providing insight into the genetic basis of mechanisms such as egg formation, antioxidant stress defense, and xenobiotic metabolism. 相似文献
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